We have identified a group of ~20 neurons that can be activated on-demand using Drosophila genetics. The sleep observed during activation of these neurons meets the historical definition for identifying sleep. Our data highlight the importance of these neurons for regulating sleep. In this proposal we will use live-cell imaging and in vivo electrophysiological recording from Drosophila brains to define the properties of these neurons in the intact brain. The ability to use Drosophila genetics to induce sleep provides a unique opportunity to examine whether sleep can be used as a therapeutic for slowing or attenuating cognitive impairments associated with degenerative diseases. Thus, we will determine whether inducing sleep in Drosophila models of Parkinson's and Alzheimer's disease can offset deficits in cognitive behavior. PUBLIC HEALTH RELEVANCE: Insufficient sleep and sleep disruption result in increased morbidity, mortality and may accelerate cognitive impairments during neurodegenerative disease. We propose to use genetics to functionally evaluate sleep promoting neurons during health and disease. We will determine whether sleep can mitigate or attenuate pathology in animal models of Alzheimer's and Parkinson's disease.